PDF(Pubmed)
Abstract：
Depression is a chronic, severe, and often life-threatening neurological disorder. It not only causes depression in patients and affects daily life but, in severe cases, may lead to suicidal behavior and have adverse effects on families and society. In recent years, it has been found that sub-anesthetic doses of ketamine have a rapid antidepressant effect on patients with treatment-resistant depression and can significantly reduce the suicidal tendencies of patients with major depressive disorder. Current studies suggest that ketamine may exert antidepressant effects by blocking NMDAR ion channels, but its anesthetic and psychotomimetic side effects limit its application. Here, we report efforts to design and synthesize a novel series of ketamine derivatives of NMDAR antagonists, among which compounds 23 and 24 have improved activity compared with ketamine, introducing a new direction for the development of rapid-acting antidepressant drugs.
摘要：
抑郁症是慢性的,严重,经常危及生命的神经系统疾病。它不仅会导致患者抑郁，影响日常生活，而且，在严重的情况下，可能导致自杀行为,对家庭和社会产生不良影响。近年来,研究发现,亚麻醉剂量氯胺酮对难治性抑郁症患者具有快速的抗抑郁作用,并能显著降低重度抑郁症患者的自杀倾向。目前的研究表明，氯胺酮可能通过阻断NMDAR离子通道发挥抗抑郁作用，但它的麻醉和精神模拟副作用限制了它的应用。这里,我们报告了设计和合成一系列新型NMDAR拮抗剂氯胺酮衍生物的努力，其中化合物23和24与氯胺酮相比活性提高，为速效抗抑郁药物的发展开辟了新的方向。
